The goal of this investigation is to study the mechanisms by which endogenous pyrogen acts upon the thermoregulatory centers of the brain to alter the level at which body temperature is regulated - fever. We are interested in the route by which pyrogen enters the brain and whether it acts on neural tissue to produce prostaglandin E. We further wish to ascertain whether PGE is an essential intermediary in the fever pathway and whether other protein dependent steps are involved prior to the genesis of fever. By observing and quantifying the alterations in PGE levels in cerebrospinal fluid under a variety of natural and pathophysiological conditions, and correlating them with the thermoregulatory responses of rabbits measured by partitional calorimetry, we hope to answer these questions. Several hypotheses are outlined in the proposal together with protocols and techniques to test their validity.